Schwartz, Gregory G, Szarek, Michael, Bittner, Vera A, Diaz, Rafael, Goodman, Shaun G, Jukema, J Wouter, Landmesser, Ulf, López-Jaramillo, Patricio, Manvelian, Garen, Pordy, Robert et al (show 5 more authors)
(2021)
Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol.
Journal of the American College of Cardiology, 78 (5).
pp. 421-433.
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Lipoprotein(a) and Benefit of PCSK9 Inhibition in Patients With Nominally Controlled LDL Cholesterol.pdf - Author Accepted Manuscript Download (1MB) | Preview |
Abstract
<h4>Background</h4>Guidelines recommend nonstatin lipid-lowering agents in patients at very high risk for major adverse cardiovascular events (MACE) if low-density lipoprotein cholesterol (LDL-C) remains ≥70 mg/dL on maximum tolerated statin treatment. It is uncertain if this approach benefits patients with LDL-C near 70 mg/dL. Lipoprotein(a) levels may influence residual risk.<h4>Objectives</h4>In a post hoc analysis of the ODYSSEY Outcomes (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) trial, the authors evaluated the benefit of adding the proprotein subtilisin/kexin type 9 inhibitor alirocumab to optimized statin treatment in patients with LDL-C levels near 70 mg/dL. Effects were evaluated according to concurrent lipoprotein(a) levels.<h4>Methods</h4>ODYSSEY Outcomes compared alirocumab with placebo in 18,924 patients with recent acute coronary syndromes receiving optimized statin treatment. In 4,351 patients (23.0%), screening or randomization LDL-C was <70 mg/dL (median 69.4 mg/dL; interquartile range: 64.3-74.0 mg/dL); in 14,573 patients (77.0%), both determinations were ≥70 mg/dL (median 94.0 mg/dL; interquartile range: 83.2-111.0 mg/dL).<h4>Results</h4>In the lower LDL-C subgroup, MACE rates were 4.2 and 3.1 per 100 patient-years among placebo-treated patients with baseline lipoprotein(a) greater than or less than or equal to the median (13.7 mg/dL). Corresponding adjusted treatment hazard ratios were 0.68 (95% confidence interval [CI]: 0.52-0.90) and 1.11 (95% CI: 0.83-1.49), with treatment-lipoprotein(a) interaction on MACE (P<sub>interaction</sub> = 0.017). In the higher LDL-C subgroup, MACE rates were 4.7 and 3.8 per 100 patient-years among placebo-treated patients with lipoprotein(a) >13.7 mg/dL or ≤13.7 mg/dL; corresponding adjusted treatment hazard ratios were 0.82 (95% CI: 0.72-0.92) and 0.89 (95% CI: 0.75-1.06), with P<sub>interaction</sub> = 0.43.<h4>Conclusions</h4>In patients with recent acute coronary syndromes and LDL-C near 70 mg/dL on optimized statin therapy, proprotein subtilisin/kexin type 9 inhibition provides incremental clinical benefit only when lipoprotein(a) concentration is at least mildly elevated. (ODYSSEY Outcomes: Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab; NCT01663402).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ODYSSEY Outcomes Committees and Investigators, Humans, Cardiovascular Diseases, Lipoprotein(a), Aged, Middle Aged, Female, Male, Cholesterol, LDL, Acute Coronary Syndrome, Antibodies, Monoclonal, Humanized, PCSK9 Inhibitors |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 13 Oct 2023 10:20 |
| Last Modified: | 13 Oct 2023 10:20 |
| DOI: | 10.1016/j.jacc.2021.04.102 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3173689 |
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